Emicizumab enhances thrombus formation in vitro under high shear flow conditions in whole blood from patients with type 1 and type 3 von Willebrand disease.

Abstract

INTRODUCTION:

Type 1 and type 3 von Willebrand disease (VWD) are caused by partial and complete, quantitative deficiency of von Willebrand factor (VWF), respectively, and factor (F)VIII/VWF complex concentrates are used for haemostatic treatment. Emicizumab, mimics activated FVIII, reduces bleeding in haemophilia A patients. The effects of emicizumab on haemostasis in both types of VWD remain to be fully established, however.

AIM:

To examine the effects of emicizumab on thrombogenesis in type 1 and type 3 VWD.

PATIENTS/METHODS:

Perfusion chamber experiments under high shear conditions (2500 s-1 ) combined with immunostaining were performed using whole blood samples from patients with type 1 (VWF:Ag 25 U/dl) and type 3 VWD (<1.0 U/dl).

RESULTS:

The addition of FVIII (1 U/ml) to type 1 blood did not affect thrombus formation, whilst supplementation with VWF (1.6 U/ml) or FVIII/VWF (1 U/ml/1.6 U/ml) enhanced thrombogenesis to a similar extent. FVIII/VWF promoted thrombus formation significantly more than VWF alone, however, in type 3 blood. Emicizumab (100 μg/ml) augmented thrombus formation in type 3 blood compared to FVIII, and this potency seemed to be somewhat greater than that of VWF. Surface coverage of formed thrombus in type 3 VWD was less than that in type 1 VWD, but thrombus height was comparable in both. The addition of emicizumab to type 3 blood enhanced thrombin generation and fibrin formation compared to control IgG.

CONCLUSION:

Emicizumab promoted mechanisms of thrombus formation in vitro in type 3 and type 1 VWD, suggesting the possibility of alternative therapeutic protocols in these patients.

• Authors: Hiroaki Yaoi, Yasuaki Shida, Kenichi Ogiwara, Takehisa Kitazawa, Midori Shima, Keiji Nogami
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 28 Issue 5 Pg. 694-701 (Sep 2022) ISSN: 1365-2516 [Electronic] England
• PMID: 35478475 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Bispecific
• Antibodies, Monoclonal, Humanized
• von Willebrand Factor
• emicizumab
• Factor VIII

Topics

• Antibodies, Bispecific
• Antibodies, Monoclonal, Humanized
• Factor VIII (therapeutic use)
• Humans
• Thrombosis (drug therapy)
• von Willebrand Disease, Type 1
• von Willebrand Disease, Type 3 (drug therapy)
• von Willebrand Diseases (drug therapy)
• von Willebrand Factor (therapeutic use)